A Phase II Trial Evaluating an Organ-conserving Strategy by Radiochemotherapy for Muscle-infiltrative Bladder Cancer

Not Applicable

Active, not recruiting

• Conditions: Infiltrating Bladder Urothelial Carcinoma
• Interventions: Other: Radiation + cisplatin + gemcitabine; Other: Radiation + cisplatin

• Registration Number: NCT01495676
• Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary

If radical cystectomy remains the standard of care for muscle invasive bladder cancer, consequences of this surgical procedure are often harsh. Over the past years, concurrent chemo-radiotherapy has imposed itself as an alternative treatment. Published data on concomitant radiochemotherapy (radiotherapy/cisplatin or radiotherapy/cisplatin/5-fluorouracil combinations) showed local control rates with bladder preservation at 5 years ranging from 40% to 65% according to the disease stage, and overall survival probabilities ranging from 40% to 50% at 5 years. In order to improve local and systemic prognosis, evaluation of other chemotherapy agents with higher radiosensitizing effect, such as gemcitabine, is justified. Gemcitabine possesses its own anti-cancer activities on urothelial diseases and has a synergetic activity with cisplatin. The investigators completed a monocenter phase I study combining radiotherapy, cisplatin, and twice-weekly gemcitabine, and determined a recommended dose of gemcitabine 25 mg/m². The objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.

Detailed Description

The objective of the present study is to evaluate the combination of radiotherapy + cisplatin + gemcitabine in terms of disease-free survival in non metastatic muscle invasive urothelial cancer patients.

Study Timeline

• Study Start: 2011-07-06
• Study First Submitted: 2011-12-14
• Study First Submitted QC: 2011-12-16
• Study First Posted: 2011-12-20
• Primary Completion: 2022-07-25
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-05
• Last Update Posted: 2023-12-06
• Study Completion: 2025-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

• Muscle invasive urothelial cancer (front line or following the progression of a superficial tumor), pT2-pT3 stage without lymphatic impairment (N0) and without detectable metastases (M0). An optimal macroscopic resection (TURB) have to be performed
• The proof of invasive tumor to the muscle should be brought by a transurethral resection under anaesthesia less than 8 weeks before or, in the absence, by superficial biopsies and formal imaging. Multiples biopsies in the bladder must also be performed.
• Age ≥ 18 years
• Life expectancy ≥ 6 months
• Kanorfsky index ≥ 70 % (WHO 0, 1, 2)
• Biological criteria: neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3, haemoglobin ≥ 10 g/dl, creatinine clearance > 60 ml/mn
• No distant metastases (Thorax, abdomen, and pelvic CT-scan, bone scan)
• Efficient contraception for premenopausal women, maintained during the whole treatment and up to two months after the completion of radiotherapy.
• No radiotherapy or chemotherapy history except for in situ bladder lesions.
• No carcinological history except for non melanoma skin tumours, in situ uterine cervix cancer
• No contraindication to gemcitabine or cisplatin.
• No contraindication to radiotherapy
• Information letter and informed consent signed
• Patient covered by social security

Exclusion Criteria

• Bladder tumors without any muscle infiltration
• Epidermoid carcinoma or adenocarcinoma
• Distance metastases or extrapelvic node positivity
• Severe digestive history (ulcerative colitis, complicated diverticulitis)
• Pregnancy and breast feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Radiotherapy + cisplatin + gemcitabine	Radiation + cisplatin + gemcitabine	-
Radiotherapy + cisplatin	Radiation + cisplatin	-

Primary Outcome Measures

Name	Time	Method
Disease-free survival	Two years after the end of the complete therapeutic sequence	The time to relapse is defined as the time from the date of randomisation to the date of the first event. Time to relapse for patients without any event (local, regional, distance, or death) will be censored at the date of latest information.

Secondary Outcome Measures

Name	Time	Method
Acute and late toxicities	Up to 5 years	Acute and late toxicities will be scored according to the NCI-CTC v4.0.
Overall survival	Up to 5 years	The time to death is defined as time from the randomization to the date of death from any cause, or to the date on which latest information is obtained.
measurement of Quality of life	Up to 5 years	Questionnaires QLQ C30 + QLQ-BLM30 + QLQ-ELD15 + Oncodage
Correlation between lymphocyte apoptosis and severity of late toxicities.	Up to 5 years	Before starting radiotherapy, 5ml of blood will be sampled in a 5ml heparinised tube to prospectively measure the rate of CD8 radio-induced lymphocyte apoptosis before any radiotherapy treatment. A correlation between the low rate of lymphocyte apoptosis and the severity of late toxicities will be studied to confirm the predictive power of this biological test on radio-induced side-effects.

Trial Locations

Locations (12)

Institut Bergonié; 🇫🇷 Bordeaux, France

Centre azuréen de Cancérologie; 🇫🇷 Mougins, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

CRLC GF Leclerc; 🇫🇷 Dijon, France

Centre Francois Baclesse; 🇫🇷 Caen, France

Hopital Henri Mondor; 🇫🇷 Créteil, France

CRLC Val d'Aurelle-Paul Lamarque; 🇫🇷 Montpellier, France

Hopital saint Louis; 🇫🇷 Paris, France

Institut de Cancérologie Lucien Neuwirth; 🇫🇷 Saint-Priest-en-Jarez, France

Centre Alexis Vautrin; 🇫🇷 Vandœuvre-lès-Nancy, France

HEGP; 🇫🇷 Paris, France

Clinique Patseur; 🇫🇷 Toulouse, France